The primary long-term objective of our program is to gain greater understanding of pathophysiological events in thromboembolic vascular disease, with a view to either the development of new therapeutic concept or the improvement of old. Substantial progress in furthering such understanding has resulted from our development of a new methodology, termed plasma fibrinogen chromatography, for the quantification of plasma of fibrinogen-fibrin derivatives resulting from such pathophysiological events as thrombosis, intravascular coagulation, blood hypercoagulability or fibrinolysis. Since each such event causes characteristic alteration in the proportions and absolute amount of such derivatives, the new methodology provides hitherto unobtainable data on patient disease status. Such methodology is particularly adapted to investigation of patients with organ infarction, e.g., cerebral infarction or myocardial infarction, to the measurement of drug induced thrombogenicity, e.g., patients receiving oral contraceptive medication, to the control of anticoagulant and thrombolytic therapies since it provides a measure of drug action on the disease process itself and is also of considerable utility in conjunction with more conventional methods, e.g., studies of plasma inhibitor concentrations, conventional blood coagulation methodology, etc., in definition of disease mechanisms. Significant correlation between the seral use of our new laboratory assays and clinical outcome in acute myocardial infarction and acute cerebral thrombosis are now emerging from our natural disease studies. Thus, this data demonstrates that the long-term disturbance of blood coagulation and plasma fibrinolytic enzyme system function developing in some patients with these disorders appears to be of significant deleterious effect.